Failed central nervous system prophylaxis in children with acute lymphoblastic leukaemia: treatment and outcome

Isolated CNS relapse occurred as a first event in 23 (6%) of 354 children with acute lymphoblastic leukaemia (ALL) who shortly after achieving remission had been treated with craniospinal irradiation or cranial irradiation and intrathecal methotrexate. CNS relapse occurred at a median time of 79 weeks from diagnosis and in three cases was asymptomatic, being diagnosed on routine lumbar puncture at completion of maintenance therapy. CNS remission was achieved with weekly intrathecal methotrexate in all but two cases who died in relapse. A second course of radiotherapy was given in 12 cases; at the time of relapse in three and delayed from 14-170 weeks later in nine. Intensified systemic chemotherapy was used in 13 patients and all but three continued on regular maintenance intrathecal methotrexate. Disease free remission following CNS relapse ranged from 9 to 366 weeks (median 76 weeks) with subsequent relapses occurring in the testis, CNS and in particular the bone marrow. Survival after relapse ranged from 11 to 476 weeks (median 92); seven patients are alive; four in continued remission, two with recurrent but controlled CNS disease, and one in remission following bone marrow transplant after subsequent marrow relapse. Recurrent CNS disease was significantly less frequent in patients who were reirradiated. It appears that long-term survival is possible after isolated CNS relapse but that further intensification of systemic chemotherapy and possibly chemo-radiotherapy and bone marrow transplant will be required to reduce the high risk of subsequent bone marrow relapse.